title: Impact of synthetic and biologic disease-modifying antirheumatic drugs on antibody responses to the AS03-adjuvanted pandemic influenza vaccine: a prospective, open-label, parallel-cohort, single-center study.
abstract: OBJECTIVE
  To identify the determinants of antibody responses to adjuvanted split influenza A (H1N1) vaccines in patients with inflammatory rheumatic diseases.
  
  
  METHODS
  One hundred seventy-three patients (82 with rheumatoid arthritis, 45 with spondylarthritis, and 46 with other inflammatory rheumatic diseases) and 138 control subjects were enrolled in this prospective single-center study. Controls received 1 dose of adjuvanted influenza A/09/H1N1 vaccine, and patients received 2 doses of the vaccine. Antibody responses were measured by hemagglutination inhibition assay before and 3-4 weeks after each dose. Geometric mean titers (GMTs) and rates of seroprotection (GMT≥40) were calculated. A comprehensive medical questionnaire was used to identify the determinants of vaccine responses and adverse events.
  
  
  RESULTS
  Baseline influenza A/09/H1N1 antibody levels were low in patients and controls (seroprotection rates 14.8% and 14.2%, respectively). A significant response to dose 1 was observed in both groups. However, the GMT and the seroprotection rate remained significantly lower in patients (GMT 146 versus 340, seroprotection rate 74.6% versus 87%; both P<0.001). The second dose markedly increased antibody titers in patients, with achievement of a similar GMT and seroprotection rate as elicited with a single dose in healthy controls. By multivariate regression analysis, increasing age, use of disease-modifying antirheumatic drugs (DMARDs) (except hydroxychloroquine and sulfasalazine), and recent (within 3 months) B cell depletion treatment were identified as the main determinants of vaccine responses; tumor necrosis factor α antagonist treatment was not identified as a major determinant. Immunization was well tolerated, without any adverse effect on disease activity.
  
  
  CONCLUSIONS
  DMARDs exert distinct influences on influenza vaccine responses in patients with inflammatory rheumatic diseases. Two doses of adjuvanted vaccine were necessary and sufficient to elicit responses in patients similar to those achieved with 1 dose in healthy controls.
authors.affiliation: University Hospitals of Geneva and University of Geneva, Geneva, Switzerland. cem.gabay@hcuge.ch
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
authors.forename: Michael
authors.initials: M
authors.lastname: Bel
authors.forename: Christophe
authors.initials: C
authors.lastname: Combescure
authors.forename: Camillo
authors.initials: C
authors.lastname: Ribi
authors.forename: Sara
authors.initials: S
authors.lastname: Meier
authors.forename: Klara
authors.initials: K
authors.lastname: Posfay-Barbe
authors.forename: Stéphane
authors.initials: S
authors.lastname: Grillet
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Seebach
authors.forename: Laurent
authors.initials: L
authors.lastname: Kaiser
authors.forename: Werner
authors.initials: W
authors.lastname: Wunderli
authors.forename: Pierre-André
authors.initials: PA
authors.lastname: Guerne
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D018501:Antirheumatic Agents / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D025241:Spondylarthritis / Q000188:drug therapy / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D018501:Antirheumatic Agents; D007252:Influenza Vaccines; D014409:Tumor Necrosis Factor-alpha